Lymphangitis carcinomatosis (LC) is a rare and often fatal form of pulmonary metastases. Author describes this as a case of left sided malignant pleural effusion with unknown primary which after follow up of two months developed lymphangitis carcinomatosis on right side. Despite extensive search of literature author could not find any information to explain the occurrence of lymphangitis carcinomatosis as in this case where the primary could not be traced. There has been literature on the association of lymphangitis carcinomatosis with pleural effusion, but there has been no literature reporting the occurrence of lymphangitis carcinomatosis after or as a complication of malignant pleural effusion.

Case Report

A fifty year-old male patient was admitted to the department of pulmonary medicine at a teaching hospital in Lucknow, India with a three months’ history of progressive shortness of breath. He complained of dyspnoea both at rest and on exertion and a decrease in his functional status. He admited to weight loss of approximately 10 Kg over 6 months and had anorexia and malaise. He denied fever, cough, chest pain, haemoptysis, wheezing, palpitations, hoarseness, orthopnea, and paroxysmal nocturnal dyspnoea. The patient denied he had significant past medical history and currently took no medications. The patient had a thirty pack years history of tobacco smoking, and had no occupational or tuberculosis exposure. The family history was also non contributory. Examination showed a slightly malnourished man, afebrile, pulse rate of 98/min, respiratory rate of 30/min and blood pressure of 140/88mm of Hg. There were no pitting oedema, cyanosis, or clubbing of fingers and no peripheral lymphadenopathy. Abdominal examination was normal without any organomegaly. Neurological examination was within normal limits. Respiratory system examination showed decreased tactile fremitus on left side with stony dull note on percussion. On auscultation the breath sounds were markedly reduced on left side.

A total of 6 litres of pleural fluid was aspirated in four sittings spread over 5 days. The ultrasonography of abdomen/pelvis including prostate, and upper GI endoscopy were normal. Bone marrow was normal. Fibre optic bronchoscopy was within normal limits. Despite all attempts to find the primary, it proved to be futile. He was put on chemotherapy regimen i.e. standard dose gemcitabine and cisplatin. Due to recurrent refilling of pleural fluid, palliative measures in the form of intercostals tube drainage was also done. Once his drainage through the tube had substantly decreased an attempt of pleurodesis was tried with doxycycline but did not succeed. During the course of chemotherapy and follow up, he showed no signs of improvement and after the third cycle of chemotherapy he started complaining of breathlessness on exertion and dry cough. A repeat X-ray chest showed reticulonodular pattern on right side with pleural thickening on the left side.

Further a high resolution CT was done and revealed features in favour of lymphangitis carcinomatosis (LC) on the right side (interlobular septal thickening, peribronchovascular thickening; centrilobular peribronchovascular thickening) (fig 2). Once again an attempt to find the primary tumour was unsuccessful.

Discussion

Malignant pleural effusions are caused most commonly by carcinomas of the lung, breast, gastrointestinal tract or ovary and by lymphomas. In male patients about half of malignant effusions are caused by lung cancer, 20% by lymphomas or leukaemia, 7% from gastrointestinal primaries, 6% from genitourinary primaries, and 11% from tumours of unknown primary site (1).

Lymphangitis carcinomatosis (LC) refers to the diffuse infiltration and obstruction of pulmonary parenchymal lymphatic channels by tumour. Lymphangitis carcinomatosis is a rare, aggressive and often fatal form of pulmonary metastases (2). Various neoplasms can cause lymphangitis carcinomatosis, but 80% are adenocarcinoma. The most common primary sites are breast, lungs, colon and stomach (3-5). Other sources include the pancreas, thyroid, cervix, prostate, larynx and metastatic cancer from unknown primary cancer.Pathophysiology for LC to occur happens as a result of the initial haematogenous spread of tumour to the lungs, with subsequent malignant invasion through the vessel wall into the pulmonary interstitium and lymphatics. Tumour then proliferates and easily spreads through these low-resistance channels (6). Less commonly, direct infiltration occurs as a result of contiguous mediastinal or hilar lymphadenopathy or an adjacent primary bronchogenic carcinoma. Patients with lymphangitis carcinomatosis usually have progressive dyspnoea and a dry cough.

Chest radiography is usually the first examination performed to detect pulmonary metastases. The typical radiographic pattern consists of thickened interlobular septa (5-10 mm or smaller) and bronchovascular markings of irregular contour .The pattern is more obvious in the lower lobes of both lungs. Hilar and mediastinal lymphadenopathy are present in 20-40% of patients, and pleural effusions are present in 30-50%. Early diagnosis of lymphangitis carcinomatosis can be difficult with x-ray findings, and may be normal in 30-50% of proven cases.

High-resolution CT (HRCT) is the modality of choice for demonstrating the presence and extent of lymphangitis carcinomatosis (7-9). Although the HRCT appearances of LC are non-specific, the observation of certain features in a symptomatic patient with an appropriate history of malignancy is highly suggestive of LC, and further investigation is generally not required. HRCT findings include the following: irregular, nodular, and/or smooth interlobular septal thickening; thickening of the fissures due to involvement of the lymphatics concentrated in the sub pleural interstitium; preservation of normal parenchymal architecture at the level of the secondary pulmonary lobule; peribronchovascular thickening; centrilobular peribronchovascular thickening, which predominates over interlobular septal thickening in a minority of patients; polygonal arcades or polygons with prominence of the centrilobular bronchovascular bundle in association with interlobular septal thickening (50%); mediastinal and/or hilar lymphadenopathy (30-50%); and pleural effusions (30-50%) (7-10). The differential diagnosis of LC includes sarcoidosis and other chronic interstitial lung diseases such as silicosis, coal worker’s pneumoconiosis, extrinsic allergic alveolitis (hypersensitivity pneumonitis), and cryptogenic fibrosing alveolitis, as well as other neoplasms such as lymphoma and Kaposi sarcoma. Most of these diagnoses can be excluded on the basis of the clinical findings alone. The relative absence of polygons and the presence of architectural distortion at the level of the secondary pulmonary lobule strongly suggest fibrosis rather than LC. Furthermore, parenchymal involvement in sarcoidosis is typically more central and/or perihilar and more bilaterally symmetric than in LC. LC never appears as honeycombing, and sarcoid granulomas are often subpleural (9). Miliary metastases may appear identical to miliary tuberculosis. Transthoracic needle aspiration has a positive yield of 85-95% in the evaluation of pulmonary nodules, but the yield is lower with lymphangitic tumour spread like that in LC, which usually requires transbronchial biopsy or thoracoscopic wedge resection for the histologic diagnosis.